Download Movement Disorders and Extrapyramidal System

Movement Disorders and
Extrapyramidal System
Doç. Dr. Sibel Ertan
İ.Ü. CTF. Nöroloji ABD.
Motor System
•
•
•
•
•
I. neuron (corticospinal pathway)
Extrapyramidal system (basal ganglia)
Cerebellum
Loops for praxis
II. neuron: Anterior horn cells of the spinal cord
Cranial cell nuclei in the brain stem
• Peripheral nerve, motor cranial nerves
• Neuromuscular junction
• Muscle
Definition
Neurologic syndromes in which there is either an
excess of movement, or a paucity of voluntary
and automatic movements unrelated to
weakness or spasticity.
Most movement disorders are associated
with pathologic alterations in the
basal ganglia or their connections.
But disorders of the
• Cerebellum or its pathways
• Cerebral cortex
• Thalamus
• Brain stem
• Spinal cord
• Peripheral nerves
may also cause several movement
disorders.
Cerebral cortex
Thalamus
Basal ganglia
Cerebellum
Dopaminergic
system
Dopaminergic
system
Spinal cord
Basal Ganglia
Caudate
Thalamus
Putamen GPe GPi
STN
SNr
SNc
Basal ganglia
subcortical nuclei:
caudate
putamen
globus pallidus
caudate,
putamen &
globus pallidus
are named
corpus striatum
Caudate
&putamen are
named
striatum
globus pallidus &
putamen are
named lentiform
nuclei
Definition
The term extrapyramidal system, coined by
British neurologist Kinnier Wilson, refers to
the basal ganglia and an array of brain
stem nuclei (red nucleus, reticular
formation etc.) to which they are
connected.
Striatum (caudate+putamen) is the
principle receptive structure of the
basal ganglia.
Globus pallidus is the principle output
structure of the basal ganglia.
SENSORY-MOTOR LOOP
Cerebral cortex
Somatic sensory
Primary motor
Premotor
Supplementary motor
Thalamic nuclei
Putamen
Gpi
SNr
Ventral
lateral
ASSOCIATIVE - LOOP
Cerebral cortex
Thalamic nuclei
Posterior parietal
Premotor
Prefrontal
Caudate
(head)
SNr
Gpi
Ventral
ant.,Dorsal
medial
LIMBIC - LOOP
Cerebral cortex
Medial, lateral
temporal lobs,
hippocampal form.,
Ant. cingulate,
Orbitofrontal cortex
Thalamic nuclei
Ventral
Striatum
caudate
(head)
Ventral
Pallidum
Gpi
SNr
Dorsomedial,
Ventral
anterior
OCULOMOTOR - LOOP
Cerebral cortex
Thalamic nuclei
Posterior parietal
Prefrontal
Frontal eye field
caudate
(body)
SNr
Gpi
Ventral
ant., Dorsal
medial
• Diseases of the basal ganglia are associated with
abnormal involuntary movements that typically occur at
rest and disappear in sleep.
• They are generally divided into two categories:
Hyperkinetic and hypokinetic
• The hyperkinetic variety is seen in such disorders as
chorea, athetosis, ballism, dystonia, tremor, and tics.
• The hypokinetic variety is seen largely in Parkinson’s
disease.
• Following anatomic loci for pathology are agreed on:
- Substantia nigra in Parkinson’s disease
- Caudate nucleus in chorea
- Subthalamic nucleus in ballism
- Caudate or lentiform nucleus (especially putamen)
in dystonia
Hypokinetic Disorders
• Parkinsonism
Six cardinal features:
1. Tremor at rest
2. Rigidity
3. Bradykinesia-hypokinesia
4. Flexed posture
5. Loss of postural reflexes
6. Freezing phenomenon
• Tremor, rigidity, and flexed posture are
referred positive phenomena.
• Bradykinesia, loss of postural reflexes,
and freezing are negative phenomena.
Rest Tremor
• 4-5 Hz
• Present in the extremities, almost always distally
• Classic “pill-rolling” tremor involves the thumb
and the forefinger
• Rest tremor disappears with action but
reemerges as the limb maintain a posture.
• Rest tremor is also common in the lips, chin, and
tongue
• Rest tremor of the hands increases with walking
• Stress worsens the tremor
Rigidity
• Increased resistance (muscle tone) to
passive movement elicited when the
exami.ner moves the patient’s limbs, neck
or trunk
• Equal in all directions
• The underlying tremor may cause
“cogwheeling”
Flexed posture
• Commonly begins in the arms and
spreads to involve the entire body
• Striatal hand
• Striatal toe
• Lateral tilting of the trunk is common
Bradykinesia
• Slowness of movement, difficulty in
initiating a movement, and loss of
automatic movement
• Hypokinesia is the reduction in amplitude
of movement
Loss of postural reflexes
• Pulltest is positive
• With progress of the disease frequent
fallings
• The patient collapses into the chair on
attempting to sit down (sitting en bloc)
Freezing
• Inability to perform active movements
(motor block)
• Often involves the legs when walking but
can also involve eyelid opening,speaking
and writing.
The many causes of parkinsonism are
divided into four categories:
1.Idiopathic
2. Symptomatic
3. Parkinson-plus syndromes
4. Heredodegenerative diseases
The core biochemical pathology in
parkinsonism is decreased dopaminergic
neurotransmission in the basal ganglia.
• Degeneration of the nigrostriatal dopamine system
• Degeneration of the striatum with loss of dopamine
receptors
• Drug induced parkinsonism as the result of blockade of
dopamine receptors.
Nigral Dopaminergic Neuron Terminals and
Striatal Receptors
Parkinson’s
Disease
Parkinson-plus
Syndromes
Drug-induced
Parkinsonizm
Parkinson’s disease (primary parkinsonism)
• Degeneration of the neuromelanin-containing neurons in
the brain stem, especially in substantia nigra pars
compacta and in the locus ceruleus.
• Many of the surviving neurons contain eosinophilic
cytoplasmic inclusions known as Lewy bodies.
• By the time symptoms appear, the substantia nigra
already has lost about 60% of dopaminergic neurons
and the dopamine content in the striatum is about 80%
less than normal.
Parkinson’s disease (primary parkinsonism)
• PD makes up approximately 80% of cases of
parkinsonism.
• Mean age at onset in both sexes is 55 years
(range:20-80).
• Male/female = 3/2.
• Prevalence ≈ 160/100.000 and incidence 20/100.000/yr.
• The cause of PD is unknown.
Parkinson’s disease (primary parkinsonism)
Treatment
• Treatment is aimed at controlling symptoms because no
drug or surgicl approach unequivocally prevents
progression of PD.
• Treatment is lifelong.
• Treatment includes pharmacotherapy, physiotherapy
and surgery.
Parkinson’s disease (primary parkinsonism)
Treatment
Therapeutic choices for Parkinson’s disease
Medications
Dopamine precursor: levodopa (LD)±carbidopa or benserazide
Dopamine agonists: bromocriptine, pergolide, pramipexole,
ropinirole, apomorphine, cabergoline.
Catecholamine-O-methyl transferase inhibitors:tolcapone and
entacapone.
Dopamine releaser: Amantadine.
Monoamine oxidase type B inhibitor: selegiline.
Anticholinergics:trihexyphenidyl, benztropine, biperidene...
Antihistaminics:diphenhydramine, orphenadrine, phenindamine
Parkinson’s disease (primary parkinsonism)
Treatment
Therapeutic choices for Parkinson’s disease
Surgery
Ablative surgery:Thalamotomy, pallidotomy.
Restorative surgery:Embryonic dopaminergic tissue
transplantation
Deep brain stimulation:Thalamic stimulation, pallidal
stimulation, subthalamic stimulation
Parkinson’s disease (primary parkinsonism)
Treatment
• All symptomatic drugs can induce side effects, and if a
patient is not troubled socially or occupationally by mild
symptoms, dru therapy can be delayed until symptoms
become more pronounced.
• LD is the most effective drug, BUT 75% of patients have
serious complications after 5 years of LD therapy.
• Younger patients, in particular, are more likely to show
response fluctuations.
• DOPA-SPARING STRATEGY:Other antiparkinsonian
drugs should be used first to delay the introduction of
LD.
• Selegiline delays the need for LD therapy by an average
of 9 months.
Hyperkinetic Disorders
• Tremor
* Involuntary oscillations of a body part
produced by alternating or synchronous
contractions of reciprocally innervated muscles.
* Physiological tremor
These tremors are very small amplitude and are
demonstrable only by means of accelerometer.
Enhanced physiological tremor: medical
conditions, drugs, anxiety, fear…
* Essential tremor ET
Typically a postural tremor (4-12 Hz) but may
be accentuated by goal-directed movements. The site of
involvement in most cases is the hands and it is
frequently asymmetric initially.
* Parkinsonian tremor
Tremor at rest, at a frequency of 4-5 Hz, is the
most characteristic and the most prominent type of
tremor in PD, but postural and kinetic tremor are also
frequently seen. Onset of the tremor is usually in one of
the hands; rarely, it may begin in the legs.
* Intention tremor
Rhythmic involuntary oscillations that undergo
exacerbation as the hand or foot approaches the target
of a voluntary movement. It indicates involvement of the
cerebellum or its connections.
• Chorea (“dance”)
Characterized by sudden, frequent involuntary,
arrhythmic, purposeless, and quick jerks of the trunk,
extremities, and head associated with facial grimaces.
They are usually distal and of low amplitude. Causes
of chorea are hereditary, autoimmune, vascular,
metabolic, toxic, inflammatory or drug induced.
• Athetosis (“without position”)
Slow, writhing, continuous, wormlike movements of
the distal parts of the extremities, chiefly the fingers,
which show bizarre posturing.
• Ballism (“jump or throw”)
Sudden, quick, continuous, unusually violent, and
flinging in nature.
Usually confined to the contralateral vascular lesion
in the subthalamic nucleus.
• Dystonia (“bad tone”)
Twisting, slow, contorting, involuntary movement,
that is somewhat sustained and often repetitive.
Dystonia can involve any part of the body. Dystonia
is classified as (1) focal, (2) segmental, (3)multifocal,
(4) hemidystonia, (5) generalized
• Myoclonus
Sudden shock-like muscle contractions.
They can be focal, multifocal, or generalized.
Myoclonus may be regular and rhythmic like tremor,
but it is usually random and irregular like chorea.
It differs from tremor in that there are visible pauses
in between the jerks.
It differs from chorea, which is flowing and
resembles fragments of normal movements.
Tics can resemble myoclonus but are voluntarily
supressible for short periods; furthermore, an inner
buildup of tension occurs during the supression of
tics.
• Tourette syndrome
Characterized by motor and vocal tics. Motor
tics are sudden, brief, involuntary movements
involving muscles in different body parts such as
eye blinking and shoulder shrugging.
Vocal tics consist of gutteral sounds, grunts,
or verbalization of words and phrases.
Motor manifestations are often associated
with behavioral abnormalities such as attention
defisits and compulsive ritualistic behaviours.
• Akathisia
The motor activity in akathisia is described
by patients as a voluntary effort to relieve
uncomfortable sensations.
Akathisia is usually expressed as changes in
body position, standing, or pacing.
In milder forms this can be voluntarily
suppressed.
In severe cases the need for motor activity is
beyond control.
Wilson disease
(Hepatolenticular degeneration)
• Autosomal recessive disorder with the gene being
located on the long arm of chromosome 13.
• The gene encodes a copper transporting P-type ATPase
that is expressed in liver and kidney
• Two fundamental defects:
1.reduced biliary transport of copper,
2.impaired formation of plasma ceruloplasmin
• Free Cu in serum is increased
• Overflow of copper from the liver produces accumulation
in other organs, mainly in brain, kidney, and cornea .
Wilson disease
(Hepatolenticular degeneration)
• In cornea, copper is deposited close to the endothelial
surface of the Descement membrane (Kayser-Fleischer
ring; most important diagnostic feature)
• Symptoms begin between the ages of 11 and 25 years
• Wilson disease is a disorder of motor function; there are
no sensory symptoms and reflex alterations.
• Symptoms of basal ganglia damage usually predominate
but cerebellar symptoms may occasionally be in the
foreground.
• Tremors and rigidity are the most common early signs.
• Seizures can occur at any stage of the disease.
Wilson disease
(Hepatolenticular degeneration)
Treatment
• Initial phase of the treatment (toxic copper levels are
brought under control)
Penicllamine
Ammonium tetrathiomolybdate
Triethylene tetramine dihydrohloride (trientine)
• Maintenance therapy
Zinc acetate
Trientine + Zinc acetate